Core C - Metabolomics Co The purpose of this core is to provide comprehensive and state-of-the-art technologies for analyzing metabolic function of pancreatic islets to all three of the research projects in the PPG. The core will be comprised of two units with distinct expertise, but unified goals, operating at Duke and UT Southwestern Medical Center (UTSWMC), respectively. The Duke component of the core consists of a mass spectrometry (MS)-based metabolic profiling laboratory resident in the Sarah W. Stedman Nutrition and Metabolism Center. This facility currently deploys GC/MS and MS/MS to measure 90 "targeted" intermediary metabolites of known identity in 4 classes in tissue extracts and bodily fluids. These capabilities for static metabolic profiling are strongly complemented by the UTSWMC component of the core, which provides NMR-based analysis of metabolic flux via stable isotope/"mass isotopomer" technology. The combined application of the methods resident in the MS and NMR laboratories will yield metabolic "fingerprints" of islets in different functional states, and in response to genetic or other kinds of manipulations performed by each of the project teams. Each of the technologies will also play an important role in validating the safety and efficacy of new islet imaging and transcriptional activator technologies being developed in Projects 2 and 3, respectively. The two components of this core have the potential to provide extraordinary depth and detail in metabolic analysis of islets, leading potentially to new understanding of how islets fail in type 2 diabetes.